Are there treatments other than lowering eye pressure?

Take Home Points

Neuroprotection treatments will come in the future, but none is
ready now

Drugs and laser used in secondary glaucoma

“Non-traditional” treatments: what you don’t know can hurt
you

We are sometimes confronted with a patient who has obeyed all the
rules of treatment, taking drops religiously, coming for exams on time,
and still vision seems to be slowly declining. From large studies, we know
that lowering the eye pressure significantly slows the progress of
glaucoma so that most patients don’t end up impaired. However, there is a
limit to what lowering eye pressure can do. For one thing, in some persons
when we lower it too much surgically, vision gets so blurred that we have to
operate to raise it back again.

It is an important priority of our research group to develop treatments that add to
pressure lowering, that protect ganglion cells from dying by making them
less sensitive to the bad influences of glaucoma. I and many of my very
bright colleagues have spent many years working on that problem. The
word that is used for this kind of non-pressure lowering treatment is
neuroprotection, meaning protecting the nerves in the eye.

The steps that have been taken so far involve several lines of work.
First, we study how glaucoma affects human eyes, what seems to make it
better or worse, and look for clues that can be studied in controlled
laboratory research. Then, we develop models of glaucoma in individual
cells in culture dishes, in pieces of the eye studied in the lab, and in
animal models in animals that are as close to human glaucoma as possible.
In each of these, we look for pathways that lead from some starting bad
thing that glaucoma does, and step by step cause ganglion cells to die. We
have found pathways that lead to ganglion cell death. There are also
survival pathways that are activated when the injury starts and whose job
it is keep the nerve cells alive. Your glaucoma could be helped either by
blocking the death pathways or by strengthening the survival
pathways.

I’ll illustrate how far we’ve come along one pathway to point out an
approach that could be tried in human glaucoma patients quite soon. It’s
fair to say that this is the best-studied potential new treatment, but I
could list another 12 that have shown benefit all the way up to blocking
glaucoma nerve cell death in animal models. In the section How did you get
glaucoma?see section How did you get glaucoma?, we mentioned that the ganglion cell fiber is damaged in
glaucoma as it passes out of the eye through the optic nerve head. When
the fiber is injured there, its ability to carry messages from outside the
eye back to the ganglion cell in the eye is blocked (obstructed axonal
transport). The cell depends on receiving these messages every day to tell
it what is going on up at the other end of its long fiber and to reassure
it that it’s connected to the right target cells in the brain.

When the messages don’t arrive properly at the cell body, it
triggers a response left over from life in the womb. When you were a
fetus, fibers knew that they had gone to the right target cell in the
brain by receiving the right messages or neurotrophic factors (called
names like BDNF and CNTF). Baby nerve cells that didn’t receive the BDNF
message thought that they were connected incorrectly, and evolution
developed a mechanism for getting rid of these mistargeted nerve cells.
They committed suicide by a genetic program in their DNA. This cell
suicide process is called apoptosis. It sounds horrifying but it is
actually an important tool our bodies use to keep only healthy cells and
to develop correctly. In glaucoma, when the message is blocked and BDNF
levels fall in the cell body, this program is activated and the cell
commits apoptosis. We found this pathway was active in both animals and
humans with glaucoma. The logical solution would be to provide more BDNF,
which we did by inserting the gene for it into the retina of rats. Presto!
Fewer ganglion cells died in those rats with lots of BDNF. A similar
experiment worked with the factor called CNTF. The reason that’s important
is that a company has developed a way to give CNTF continuously to the eye
and is already treating some glaucoma patients with it so
see if it helps. Their ingenious system is a little capsule that can be
sewn inside the eye. This is not trivial, but certainly possible for many
eyes without interfering with vision. Inside the capsule are human cells
that are engineered to constantly produce CNTF. The recipient eye’s
defense mechanism can’t kill these cells by immune rejection, because they
are inside the capsule, but the CNTF gets out to bathe the retina. Such
capsules have been safely put in human eyes for a year or more without ill
effects. We are actively working on methods to deliver drugs that are neuroprotective to the eye
by injecting them alongside (not into) the eye in the office. This sustained delivery method
has been shown to have effects for months, so one would need only 2 deliveries per year. Furthermore,
the drug would go straight into the eye without causing side effects on the rest of body, and, patients
wouldn't have to remember to take pills.

These illustrate ways that an implanted device, gene therapy, or sustained delivery could be
used for neuroprotection in glaucoma. We and other researchers
are working very hard with some drug companies to try other approaches
that could work. For example, the same viral carrier particle that put the
CNTF into rats in our lab experiments has been used to put another gene
into the eyes of human patients with a disease called Leber’s congenital
amaurosis, with great benefit to their vision. This is called gene
therapy, and some form of it will surely be used in the future. With the
millions of glaucoma patients, there should be plenty of reason for drug
companies to help us to develop new treatments.

The problem is that we are impatient (and I’m at least as impatient
as all my patients are) for a breakthrough in neuroprotection. This leads,
however, to behavior that doesn’t make sense. For example, well before we
found out that Memantine, the failed neuroprotection drug, didn’t work,
lots of eye doctors decided to start prescribing it for their patients.
This was possible because the drug was FDA approved to treat dementia, so
it is legal to write prescriptions in what is called off-label use. This
means that using it for glaucoma is not approved by the FDA, because there
is no evidence it will help. This kind of prescribing is legal and is
frequently done, as long as the patient knows that the drug hasn’t been
shown to help their problem. My opinion, however, is that if we don’t know
it will help, how do we know it won’t hurt? Giving someone a drug without
knowing the side effects on their eye and on their glaucoma is taking a
risk without proven benefit.

But, use of nutriceuticals, herbal remedies, and
alternative treatments is another realm altogether. There is not a single
one of these treatments that has been shown
scientifically to benefit glaucoma. Vitamins were shown not to help
glaucoma in a large, controlled research study. And, when
you buy such a product, neither you nor I have any idea what is in it. I
have heard from patients taking Ginko biloba, Echinacea, St Johns’ Wort,
and fish oil that they do it because they are “natural products, and after
all, it can’t hurt, can they?” Companies or web sites that sell these
products have no extermal regulation system for what is in the product.
A study by the New York State Attorney General found that 80% of nutriceuticals had none
of the supposed beneficial ingredient in them!
We have regulations on things that we take as medicine for a reason.
Someone could cut their lawn today, put the clippings in a capsule and
sell it to you at a health store or web site as an herbal medicine. I once
had a patient tell me that he was taking a pill called “MK 801”. I was
intrigued, because I knew that a lab experiment in rats had shown benefit
to rat glaucoma by dosing them with MK801. Some enterprising
Internet site was selling a white pill labeled as this chemical to
gullible (and desperate) patients. The truth is that if the patient were
actually taking MK801, he would have died from it, since MK801 is highly toxic. Some of these herbals have bad effects that are unpredictable, like
blocking the effects of birth control pills and causing strokes. It’s not
true that "it can't hurt".

If you were
taking insulin for diabetes, would you take 10 times more one day and none
the next, without knowing which you were doing? The FDA web site lists a
similar study, titled: “Tainted Products Marketed as Dietary Supplements”
(http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/UCM236998.pdf)

One book written by a glaucoma patient for other glaucoma patients
has actively advocated the benefit of holistic and alternative treatments.
Anecdotal testimonials by individuals who claim to have been helped are
not reasons to do something. If you wish to be a supporter of the
development of truly acceptable new treatments for glaucoma, don’t waste
money on things that have no evidence to help you. Donate the money to a
research group studying future neuroprotection for glaucoma in legitimate
research laboratories.

One of the most frequently asked questions about unapproved
treatments for glaucoma is whether marijuana really helps. After all,
several states now permit use of “medical marijuana”. The bottom line is
that you don’t want to smoke or swallow pot to treat your glaucoma. It is
true that marijuana has some power to lower eye pressure. There are
several good reasons why it’s not useful. First, no one can standardize
how much potency it has—the chemicals in pot are a very complex mixture of
things called cannabinoids, and no one can figure out which single one of
them works to lower eye pressure. Second, you can’t
separate the pressure-lowering from being stoned, and you would have to be
high all day, every day to lower pressure. Third, if you smoke
it, you ruin your lungs and increase your lung cancer risk. Fourth, you’re
at risk for ingesting whatever insecticide someone put on it.

If you would like to support the cost of providing and maintaining this book with a charitable donation of any size,
please click here.